My goal is to elucidate the molecular mechanisms by which primary amines, particularly allylamine, cause myocardial cell injury. Allylamine consumption provides an excellent model of myocardiopathies in man. In pilot studies, we have observed that when rats were given allylamine in their drinking water, severe myocardial injury was evident weeks before arterial damage became manifest. Thus, contrary to what other workers have assumed, the myocardial injury induced by allylamine precedes vascular injury. We have confirmed the finding of Lalich that simultaneous consumption of monoamine oxidase inhibitors with allylamine alleviates or eliminates the severe cardiotoxicity of allylamine. This suggests that a metabolite of allylamine is the ultimate toxin. Our observation that allylamine consumption induces continuous myocardial cellular injury, necrosis and fibrous replacement before causing significant vascular injury will be examined in animals given allylamine for progressively shorter periods. Coronary arteries and myocardium will be fixed in situ by perfusion and the subcellular locus of injury determined by transmission electron microscopy. Arterial endothelium will be observed en face by scanning electron microscopy. Alterations will be quantitated by morphometric techniques. Blood pressure, myocardial blood flow and cardiac electrical activity will be monitored. Chemical parameters of injury such as electrolyte and glutathione abnormalities and cardiac enzyme deactivation will be established. Pharmacokinetics of 14C-allylamine distribution, excretion, metabolism and covalent binding will be characterized. Reactive metabolites such as allyl alcohol or allylaldehyde will be sought. Once the metabolic fate of allylamine and the nature of its cardiac toxicity are clarified, we will determine how monoamine oxidase inhibitors modulate these processes.